BINDING OF HUMAN SERUM AMYLOID-A (HSAA) AND ITS HIGH-DENSITY LIPOPROTEIN(3) COMPLEX (HSAA-HDL(3)) TO HUMAN NEUTROPHILS - POSSIBLE IMPLICATION TO THE FUNCTION OF A PROTEIN OF AN UNKNOWN PHYSIOLOGICAL-ROLE

Serum amyloid A (SAA) is an acute-phase serum protein which exists in the body in a complex with high-density lipoprotein (HDL(3)). It is in volved in chronic inflammation and neoplastic diseases in an as yet un known manner. Toward an understanding of the possible physiological ro le of SAA we initiated a study of its association with blood proinflam matory cells with which it may interact functionally in vivo. In the f ollowing we describe the binding characteristics of recombinant human SAA to human neutrophils (polymorphonuclear leukocytes; PMNLs) and the ir plasma membranes. Scatchard analysis of rSAA binding and displaceme nt curves revealed K-d in the nanomolar range. The C-terminal domain o f the protein, i.e. amino acid residues 77-104, which might reside in serum following SAA degradation and amyloid A formation, was found to inhibit efficiently the binding of the whole protein to neutrophils. T he interaction of SAA, and of its related peptides while complexed in HDL(3), with human PMNs was also studied. The results suggest that SAA may be involved, in an as yet unknown manner, in the neutrophil-assoc iated inflammatory mechanism. (C) Munksgaard 1996.